Soft wireless multimodal cardiac implantable devices for long-term investigating heart failure pathogenesis

用于长期研究心力衰竭发病机制的软无线多模式心脏植入装置

基本信息

  • 批准号:
    10735395
  • 负责人:
  • 金额:
    $ 58.12万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-09-01 至 2028-07-31
  • 项目状态:
    未结题

项目摘要

Project Summary The goal of this R01 proposal is to develop an ultra-soft, fully implantable, wireless label-free cardiac mapping and modulation system and apply it to identify chronic electrophysiological and metabolic changes and their links during heart failure (HF) development, progression, and pacing treatment in unrestrained conscious animals at cellular and whole heart levels. To achieve this, a miniaturized, mechanically compliant platform that integrates high-density, high-resolution sensing and modulation channels with wireless energy harvesting, storage, control, and data communication module is proposed. The resulting systems will greatly reduce motion artifacts and allow bidirectional high-content electrical and metabolic mapping and pacing in live animals. Those devices are innovative because they directly address the current limitations in chronically quantifying the individual roles and interplay between vital cardiac biophysical parameters during heart disease pathogenesis and will be used to fundamentally investigate the complex disease mechanisms involved in pathophysiological conditions leading to lethal HF and its therapeutic treatment. Once realized, this technology will be highly valuable to the cardiac research community. In the long term this work will enable closed-loop multiparametric cardiac mapping and pacing systems and offer new approaches to study the precise mechanisms and optimize the diagnostic and therapeutic strategies of other life-threatening heart diseases beyond HF. The three specific aims are: Aim 1 will establish ultra-soft multimodal cardiac systems for label-free cellular-resolution mapping of the excitation-contraction-metabolic waves and cardiac pacing. The mechanically compliant highly stretchable systems consist of high-density arrays (~300 channels in total) of (1) transparent microelectrodes for electrical mapping and stimulation; (2) multicolor micro-light-emitting diodes, and micro-photodetectors to excite and measure the autofluorescence of major endogenous fluorescent markers of cellular energy metabolism. Aim 2 will develop fully implantable wireless schemes for power harvesting, storage, control, and data communication to chronically operate the platforms in Aim 1 within a closed thoracic cavity in freely behaving small animals, which is beyond any possibility supported by current techniques. Graphical user interfaces will be developed for device configuration, real-time bidirectional control, data acquisition and processing. The integrated systems will be characterized, validated, and optimized by iterative benchtop measurements. Aim 3 will systematically investigate the precise mechanisms of HF pathogenesis and therapy using a battery of tests in rat models of HF. The functions of the proposed systems will be assessed in both ex vivo and in vivo studies. The implantable cardiac devices will identify the individual roles and links between local metabolic and electrical properties during different time points and stages of HF development and progression, and thoroughly evaluate the effects of cardiac-resynchronization therapy.
项目摘要 该R 01提案的目标是开发一种超软、完全植入式、无线无标签心脏标测 和调制系统,并将其应用于识别慢性电生理和代谢变化及其联系 在无限制清醒动物的心力衰竭(HF)发展、进展和起搏治疗期间, 细胞和整个心脏水平。为了实现这一点,一个小型化的,机械兼容的平台, 高密度、高分辨率传感和调制通道,具有无线能量收集、存储、控制 设计了数据通信模块。由此产生的系统将大大减少运动伪影, 允许在活体动物中进行双向高内容电和代谢标测和起搏。这些设备 创新,因为它们直接解决了目前长期量化个人角色的局限性, 在心脏病发病过程中重要的心脏生物物理参数之间的相互作用,并将用于 从根本上研究复杂的疾病机制涉及的病理生理条件,导致 致死性HF及其治疗。一旦实现,这项技术将对心脏非常有价值。 研究社区。从长远来看,这项工作将实现闭环多参数心脏标测, 起搏系统,并提供新的方法来研究精确的机制和优化诊断和 HF以外的其他危及生命的心脏病的治疗策略。这三个具体目标是: Aim 1将建立超软多模态心脏系统,用于无标记细胞分辨率标测 兴奋收缩代谢波和心脏起搏。机械顺应性高可拉伸性 系统由高密度阵列(总共约300个通道)组成(1)用于电 映射和刺激;(2)微发光二极管和微光电探测器,以激发和 测量细胞能量代谢的主要内源性荧光标记物的自发荧光。 AIM 2将开发用于能量收集、存储、控制和数据的完全植入式无线方案 通信,以便在自由活动的情况下在闭合胸腔内长期操作Aim 1中的平台 小动物,这超出了现有技术支持的任何可能性。图形用户界面将 为设备组态、实时双向控制、数据采集和处理而开发。的 集成系统将通过反复的台式测量来表征、验证和优化。 目的3将系统地研究HF发病机制和治疗的确切机制, 在HF大鼠模型中的测试。将在离体和体内两种情况下评估所提出的系统的功能 问题研究植入式心脏设备将识别局部代谢和局部代谢之间的个体作用和联系。 在HF发展和进展的不同时间点和阶段的电性能,并彻底 评价心脏起搏治疗的效果。

项目成果

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